What is the best management of Heart Failure with Reduced Ejection Fraction (HFrEF)?

From the Guidelines

The best management of Heart Failure with Reduced Ejection Fraction (HFrEF) involves a comprehensive approach centered on guideline-directed medical therapy (GDMT), starting with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor-neprilysin inhibitor (ARNI), a beta-blocker, and a mineralocorticoid receptor antagonist (MRA), as recommended by the most recent guidelines 1.

Key Components of HFrEF Management

• An ACEI like lisinopril or an ARNI such as sacubitril/valsartan, plus a beta-blocker such as carvedilol, metoprolol succinate, or bisoprolol, should be initiated and titrated to target doses as tolerated 1.
• A mineralocorticoid receptor antagonist (MRA) like spironolactone or eplerenone should be added for patients with NYHA class II-IV symptoms 1.
• For patients who remain symptomatic, sodium-glucose cotransporter-2 (SGLT2) inhibitors such as dapagliflozin or empagliflozin should be incorporated regardless of diabetes status 1.
• Diuretics like furosemide should be used as needed for volume management 1.
• In appropriate patients, consider ivabradine for persistent elevated heart rate, hydralazine/isosorbide dinitrate (especially in African American patients), or digoxin for symptom control 1.

Non-Pharmacological Approaches

• Sodium restriction (<2-3g/day) 1
• Fluid management 1
• Regular physical activity 1
• Cardiac rehabilitation 1

Rationale

This regimen is effective because it targets multiple pathophysiological mechanisms: neurohormonal activation, sodium and fluid retention, and maladaptive ventricular remodeling, as supported by recent studies 1. The most recent guidelines from 2024 1 provide the strongest evidence for the management of HFrEF, emphasizing the importance of GDMT and the addition of SGLT2 inhibitors for improved outcomes.

From the FDA Drug Label

1 INDICATIONS AND USAGE

1.1 Adult Heart Failure Sacubitril and valsartan tablets are indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure and reduced ejection fraction.

The best management of Heart Failure with Reduced Ejection Fraction (HFrEF) includes the use of sacubitril and valsartan tablets to reduce the risk of cardiovascular death and hospitalization for heart failure.

• The treatment decision should be based on clinical judgment. 2

From the Research

Management of Heart Failure with Reduced Ejection Fraction (HFrEF)

The management of HFrEF involves a combination of pharmacological and device-based therapies.

• Implantable cardioverter-defibrillators (ICDs), cardiac resynchronization (CRT), and combined (CRT-D) therapies have emerged as integral technologies in the management of select patients with HFrEF 3.
• Catheter ablation is another important strategy for managing cardiac arrhythmia in HF, demonstrating superior efficacy when compared with antiarrhythonic drug therapy alone 3.

Pharmacological Treatments

Several new pharmacological treatments have been shown to be effective in managing HFrEF, including:

• Levosimendan, which has been shown to improve left ventricle ejection fraction (LVEF%) 4.
• Omega-3, which has been shown to regulate heart rate (HR) and decrease serum level of B-type natriuretic peptide (BNP) 4.
• Angiotensin receptor-neprilysin inhibitors (ARNIs), which have emerged as the preferred strategy for inhibiting the renin angiotensin system 5.
• Sodium glucose cotransporter 2 (SGLT2) inhibitors, which have been shown to improve outcomes in patients with HF regardless of their diabetic status 5.

Treatment Sequencing

A rapid sequencing strategy has been proposed, which involves starting patients on all four foundational treatments (an angiotensin receptor-neprilysin inhibitor, a beta-blocker, a mineralocorticoid receptor antagonist, and a sodium-glucose co-transporter 2 (SGLT2) inhibitor) within 2-4 weeks 6.

• This approach is based on the principles that drugs act rapidly to reduce morbidity and mortality, and that the efficacy of each foundational therapy is independent of treatment with the other drugs 6.

Core Medical Therapies

The core medical therapies for patients with HFrEF include:

• Beta blockers
• Mineralocorticoid receptor antagonists
• Angiotensin receptor-neprilysin inhibitors (ARNIs)
• Sodium glucose cotransporter 2 (SGLT2) inhibitors 5. Additional approaches, such as ivabradine, hydralazine/isosorbide dinitrate combination, digoxin, and vericiguat, may be used as adjuncts to the core therapies in selected patients 5.